Biomedical subjects

M J Radin

Publications and source records attributed to M J Radin.

At least 19 recordsLinked to original sources

PubMed2001

Obese female SHHF/Mcc-fa(cp) rats resist antihypertensive effects of renin-angiotensin system inhibition.

Gender and obesity may influence response to pharmacological modulation of the renin-angiotensin system. We used SHHF/Mcc-fa(cp) rats to study effect of obesity and gender on the ability of an AT1 receptor antagonist to decrease blood pressure. After 2 weeks treatment with irbesartan (50 mg/kg), only lean and obese males showed significant decreases in blood pressure, while obese females were completely resistant. Lean females showed a trend toward lowering of pressure (p=0.06). However, irbesartan similarly shifted angiotensin II dose response curves to the right in all groups. Twelve weeks of irbesartan also failed to decrease blood pressure, but did significantly reduce heart weight in obese females. In untreated rats, obese females had lower plasma renin activity and serum angiotensin converting enzyme activity compared to lean males, while lean and obese females had increased urinary endothelin excretion. Despite an otherwise similar genetic background contributing to hypertension and heart failure, obese females have different patterns of humoral activation compared to lean males, which may contribute to their resistance to the depressor effects of irbesartan.

Angiotensin II↗

PubMed2001

Response: persistent perplexities.

This response to the preceding five articles highlights the stubborn persistence of the philosophical perplexities surrounding commodification in the realm of medicine and biotechnology.

Bioethical Issues↗

PubMed1999

Effect of ovariectomy and estrogen replacement on cardiovascular disease in heart failure-prone SHHF/Mcc- fa cp rats.

The importance of endogenous and exogenous estrogen levels to the development of cardiovascular disease in women in controversial. The purpose of our study was to examine the effect of estrogen on the development of hypertension, cardiac hypertrophy, ventricular function, and gene expression for atrial natriuretic peptide (ANP) and components of the renin angiotensin system in spontaneously hypertensive heart failure rats (SHHF/Mcc- facp). Development of hypertension was prevented in 3-month-old ovariectomized rats receiving subcutaneous 17 beta -estradiol implants (EST) compared to ovariectomized (OVX) and controls (CON). EST had the least left ventricular hypertrophy, CON were intermediate, and OVX had the most (P<0.05), correlating well with systolic blood pressure. OVX had significantly lower percentage V(1)myosin isoform compared to EST and CON, indicating reversion to a more immature phenotype associated with hypertrophy. Similarly, OVX had decreased percentage left ventricular shortening fraction by echocardiography compared to EST and CON. These changes were not accompanied by alterations in plasma ANP, or in expression of mRNA for left ventricular ANP, renal renin, or hepatic angiotensinogen. Serum angiotensin converting enzyme activity was lower in EST compared to CON or OVX. When 17 beta -estradiol was given to 17-month-old rats that had naturally ceased estrous cycling, there was no effect on hypertension, progression of cardiac functional decline, or survival. In conclusion, estradiol treatment given prior to the development of hypertension in SHHF prevented left ventricular hypertrophy and hypertension. Development of congestive heart failure was not delayed if 17 beta -estradiol was begun in the post-menopausal period. Effectiveness of estrogen therapy may depend on age or whether hypertension is already established at the time treatment is begun.

Animals↗

PubMed1999

Comparison of verapamil and felodipine treatment on lipid and glucose metabolism in obese female SHHF/Mcc-facp rats.

Calcium channel blockers, verapamil or felodipine, were given to genetically obese 6 and 11-month-old female SHHF/Mcc-facp (SHHF: Spontaneous Hypertension Heart Failure) rats for 8 weeks to investigate their effects on glucose and lipid metabolism and obesity. Both antihypertensive agents significantly decreased systolic blood pressure. In 11-month-old rats, verapamil treatment significantly decreased body weight after 4 weeks whereas with felodipine it was only significantly reduced after 8 weeks. In 6-month-old rats, verapamil significantly curtailed body weight gain. Subcutaneous fat depots were smaller, and abdominal fat depots were larger in verapamil rats compared to felodipine or control rats. Oral glucose tolerance tests in the 6-month-old verapamil and the 11-month-old felodipine groups showed improved glucose tolerance compared to their respective control groups. After 8 weeks of treatment, fasting plasma glucose levels were lower in 6-month-old verapamil rats compared to felodipine and control rats and were decreased by both verapamil and felodipine treatments as compared to control in 11-month-old rats. During the oral glucose tolerance test in 6-month-old rats, both fasting plasma insulin and the area under the insulin curve were increased in verapamil compared to both control and felodipine groups. When compared to controls, plasma cholesterol was increased by verapamil in both age groups, but was significantly decreased by felodipine after 8 weeks of treatment in the 11-month-old group. Plasma triglycerides increased in all control rats compared to initial levels; however, verapamil and felodipine groups showed lower triglycerides in both age groups. In 6-month-old rats, the percentages of plasma HDL significantly increased in both treatment groups as compared to control. This study shows that verapamil and felodipine depressed body weight gain in the young rats, reduced body weight in the old rats, improved lipid parameters and glucose tolerance, but had the opposite effects on body fat distribution and insulin levels in obese female SHHF rats.

Age Factors↗

PubMed1999

Comparison of irbesartan with captopril effects on cardiac hypertrophy and gene expression in heart failure-prone male SHHF/Mcc-fa(cp) rats.

Angiotensin-converting enzyme (ACE) inhibitors have proven an effective means to control hypertension and manage cardiac hypertrophy. It is presently unknown if newer specific angiotensin II subtype 1 receptor (AT1R) antagonists are as effective or more effective in treating these conditions compared with ACE inhibitors. There is evidence that these classes of drugs may affect cardiac hypertrophy by different mechanisms. This study compared the effect of irbesartan, an AT1R antagonist, with that of captopril, an ACE inhibitor, on expression of early genetic markers of cardiac hypertrophy in lean male SHHF/Mcc-fa(cp) rats. SHHF/Mcc-fa(cp) rats (n = 10/group) were given captopril (100 mg/kg/day), irbesartan (50 mg/kg/day), or placebo for 16 weeks. Irbesartan and captopril significantly reduced systolic pressure and produced similar rightward shifts in the angiotensin I dose-response curve. Renal renin gene expression was increased 8.6-fold by irbesartan and 17.7-fold by captopril. The only effect on echocardiographic findings was a similar decrease in aortic peak velocity, an index of systolic function, by both treatments. Early markers of cardiac hypertrophy were significantly attenuated by both drugs. Both drugs produced marked and equivalent reductions in left ventricular atrial natriuretic peptide (ANP) messenger RNA (mRNA) levels compared with controls. This decrease in ANP gene expression was accompanied by a decrease in plasma ANP concentration in the treatment groups. The shift from V1 to V3 myosin isozymes was similarly decreased in both treatment groups, compared with controls. These data suggest that captopril and irbesartan are similarly effective in controlling expression of genes associated with ventricular hypertrophy in heart failure-prone SHHF/Mcc-fa(cp) rat.

Angiotensin I↗

PubMed1998

Effect of ovariectomy in heart failure-prone SHHF/Mcc-facp rats.

The importance of the loss of ovarian function to the progression of hypertension and heart disease in women is controversial. We investigated whether ovariectomy would accelerate development of hypertension, congestive heart failure, and neurohumoral activation in adult spontaneous hypertension heart failure (SHHF) rats, a genetic model of heart failure. Six months after ovariectomy, no significant differences between control and ovariectomized rats were seen in systolic or diastolic blood pressure, left ventricular fractional shortening by echocardiography, or heart weight. Percent V1 myosin isozyme was significantly lower in ovariectomized rats. Northern blot analysis failed to show significant differences between groups in expression of hepatic angiotensinogen, renal renin, or left ventricular atrial or brain natriuretic peptide mRNA. In a second experiment, serial measures of systolic pressure and left ventricular shortening fractions failed to document a significant difference between control and ovariectomized rats as they developed heart failure, although there was a significant decline in shortening fraction in both groups at the age when regular estrous cycling naturally ceases. Survival time was similar between groups. In summary, ovariectomy of adult SHHF rats does not appear to affect the progression of genetically programmed hypertension and heart failure in this model.

Animals↗

PubMed1997

Verapamil accelerates the transition to heart failure in obese, hypertensive, female SHHF/Mcc-fa(cp) rats.

We sought to characterize the effects of the nonselective Ca2+ channel antagonist, verapamil, and the vascular-selective Ca2+ channel antagonist, felodipine, on obese, hypertensive, heart failure-prone, female SHHF/Mcc-fa(cp) rats. Rats were treated for < or = 2 months with verapamil (57 mg/kg/day) or felodipine (24 mg/kg/day). Blood pressures were determined at monthly intervals by the tail-cuff method. Heart weights and myosin isoforms were measured at the end of treatment. Direct cardiac effects of verapamil and felodipine were examined in electrically field stimulated, fura-2/AM-loaded cardiomyocytes. Both Ca2+ channel antagonists reduced systolic blood pressures. Verapamil, but not felodipine, increased heart weights and decreased expression of the myosin V1 isoform. In older animals, 75% of those treated with verapamil developed end-stage congestive heart failure. Age-matched control and felodipine-treated rats remained healthy. In isolated cardiomyocytes, 10(-9) M verapamil significantly reduced Ca2+ transient amplitudes but 10(-9) M felodipine did not. Both Ca2+ channel antagonists reduced blood pressures in obese, hypertensive, female SHHF rats. Verapamil, but not felodipine, produced heart failure in a large number of these animals. Differences between the in vivo effects of the two Ca2+ channel antagonists may be related to the differing effects on sarcolemmal Ca2+ influx.

Animals↗

PubMed1997

Autosomal dominant polycystic kidney disease in Persian and Persian-cross cats.

A form of autosomal dominant polycystic kidney disease (ADPKD) similar in clinical features to human ADPKD occurs in the Persian cat. We characterized the morphologic and immunohistochemical features of this disease in a colony of affected cats. Complete postmortem examinations were performed on 11 normal and 22 affected cats ranging in age from 3 months to 10 years. Kidneys were evaluated by gross and histologic examinations, ultrastructure, lectin staining, bromodeoxyuridine immunochemistry for labeling index and immunochemistry for distribution of Na/K ATPase. Feline ADPKD was characterized by variable numbers of cysts in the renal cortex and medullar. Ultrastructural examination and lectin staining suggested that cysts arose from proximal and distal nephron segments. Bromodeoxyuridine labeling demonstrated increased proliferation of epithelium lining some cysts in young cats. Immunohistochemical staining showed variable translocation of Na/K ATPase from the basolateral membranes of cyst-lining cells to the cytoplasm or luminal membranes. Cystic renal disease commonly was associated with chronic tubulointerstitial nephritis and hepatobiliary hyperplasia and fibrosis. Focal hyperplasia of renal tubular epithelium, hepatic cysts, and cardiac lesions were present in some cats. Feline ADPKD shares many morphologic and pathogenetic features with human ADPKD.

Animals↗

PubMed1996

Renal function and organic anion and cation transport during dehydration and/or food restriction in chickens.

The effect of dehydration in the presence or absence of continued food intake on renal function was evaluated in chickens. In addition, renal transport of organic anions and cations under these conditions was assessed in vitro by uptake of 14C-para-aminohippuric acid and 14C-tetraethylammonium bromide by renal slices. Water restriction with continued food intake resulted in increases in serum osmolality and serum concentrations of sodium, uric acid, calcium and total protein. If food was restricted in addition to water, only serum osmolality and sodium concentration were significantly increased after 48 hours. Dehydration with continued access to food resulted in marked decreases in extracellular fluid volume, glomerular filtration rate and effective renal plasma flow. If food was restricted during dehydration, the decrease in effective renal plasma flow was attenuated despite reductions in glomerular filtration rate and extracellular fluid comparable to that seen in dehydrated birds allowed free access to food. Transport of organic anions was significantly increased after 24 and 48 hours of water restriction, regardless of whether food was withheld. Enhanced transport of organic anions in the presence of decreased glomerular filtration rate and effective renal plasma flow during dehydration may promote precipitation of urates and nephrosis in chickens.

Animals↗

PubMed1995

An animal model of gastric ulcer due to bacterial gastritis in mice.

Conventional female BalbC mice were inoculated with Gastrospirillum-like bacteria in mouse gastric homogenate or in 5.0-microns filtrate of gastric homogenate. The bacteria were originally isolated from cheetahs with gastritis. The mice were killed 6 months, 7 months, or 1 year after inoculation. All mice became infected with Gastrospirillum-like bacteria that were confined to the gastric mucosa. Control mice, given either sterile Brucella broth, 0.22-microns filtrate of infected gastric homogenate, or uninfected gastric homogenate did not become infected with bacteria. Lesions in infected mice included severe lymphoplasmacytic gastritis (26/26 infected mice), gastric epithelial hyperplasia (25/26 infected mice), and gastric ulceration (11/26 infected mice). Neutrophilic inflammatory cell infiltrates were inconsistent. None of the uninfected control mice had Gastrospirillum-like bacteria, gastritis, gastric epithelial hyperplasia, or gastric ulceration. These results implicate Gastrospirillum-like bacteria from cheetahs in the pathogenesis of gastric ulceration. This model will be useful in investigating the mechanisms of gastric ulceration associated with bacterial gastritis.

Animals↗

PubMed1993

Animal models of bacterial gastritis: the role of host, bacterial species and duration of infection on severity of gastritis.

Gastric bacteria from cheetahs with gastritis were used to inoculate specific-pathogen free kittens and conventional mice. Helicobacter sp. and Gastrospirillum sp. colonized kittens, while only Gastrospirillum sp. colonized mice. In kittens, both bacterial species induced mild lymphofolliclar gastritis which did not change over the course of the 11 months observation period. In mice, Gastrospirillum sp. induced lymphoplasmacytic and follicular gastritis which increased in severity over 6 months and persisted for the 12 month observation period. Gastric ulcers and gastric mucosal hypertrophy were present in chronically infected mice. These results indicate that host but not bacterial factors influence the severity of gastritis, and that in mice, bacterial gastritis increases in severity with time and may lead to gastric ulceration in some individuals.

Animals↗

PubMed1993

Helicobacter acinonyx sp. nov., isolated from cheetahs with gastritis.

Four strains of a novel Helicobacter species were isolated from the stomachs of cheetahs (Acinonyx jubilatus) with gastritis. These isolates were phenotypically similar to Helicobacter pylori. The isolates were gram-negative, spiral bacteria which grew under microaerophilic conditions at 37 degrees C, but not at 25 or 42 degrees C, and produced urease, catalase, oxidase, alkaline phosphatase, and gamma-glutamyl transpeptidase. The isolates did not ferment glucose, mannitol, inositol, sorbitol, rhamnose, sucrose, melibiose, amygdalin, or arabinose; hydrolyze hippurate or indoxyl acetate; or reduce nitrate. They did not produce H2S from triple sugar iron agar, and they did not grow in the presence of 1.0% glycine or 1.5% NaCl. They were resistant to nalidixic acid and sensitive to cephalothin and metronidazole. Cells were typically 0.3 by 2.0 microns and possessed tufts of two to five sheathed, monopolar flagella. The G+C content of strain 90-119 was 30 mol%. Cluster analysis of densitometry scans of polyacrylamide protein gels revealed more than 70% similarity of the cheetah isolates to H. pylori, less than 60% similarity to Helicobacter felis, and less than 50% similarity to Helicobacter mustelae. Complete 16S rRNA sequences were determined for two of the cheetah isolates. Phylogenetic analysis was performed by comparing the cheetah sequences to those of 19 reference strains, including H. pylori, H. felis (two strains), H. mustelae, Helicobacter muridarum, "Flexispira rappini," Wolinella succinogenes, Campylobacter coli, Campylobacter concisus, Campylobacter curvus, Campylobacter fetus, Campylobacter hyointestinalis, Campylobacter jejuni, Campylobacter lari, Campylobacter rectus, Campylobacter sputorum subsp. bubulus, a Campylobacter sp. (pig isolate), [Bacteroides] gracilis, and [Bacteroides] ureolyticus.(ABSTRACT TRUNCATED AT 250 WORDS)

Acinonyx↗

PubMed1993

The effect of atrial natriuretic peptide infusion on renal haemodynamics and plasma lipoproteins in puromycin aminonucleoside nephrosis in rats.

1. The effect of continuous intravenous administration of 1 microgram/h atrial natriuretic peptide (ANP) for 4 days was studied in normal male Sprague-Dawley rats and rats made nephrotic with puromycin aminonucleoside (PA). 2. ANP infusion significantly increased urinary sodium and potassium excretion by 3 days of infusion in control rats but not in PA-treated rats. ANP infusion significantly increased glomerular filtration rate in PA-treated rats, while effective renal plasma flow was similarly decreased compared with non-infused nephrotic rats. 3. Plasma high density lipoproteins (HDL) were significantly decreased and low density lipoproteins (LDL) were increased in PA-treated rats that received ANP; HDL were increased in normal rats infused with ANP. 4. Competitive binding studies demonstrated a lower density of specific ANP receptors in glomerular membranes from rats injected with PA, while binding affinity was unchanged. 5. Infusion with exogenous ANP did not promote natriuresis in PA nephrosis despite an enhancement of glomerular filtration rate (GFR), thus suggesting that sodium retention in this model is due to a post-glomerular defect. Plasma lipoprotein composition in both normal and nephrotic rats may be affected by ANP.

Animals↗

PubMed1993

Epizootic gastritis associated with gastric spiral bacilli in cheetahs (Acinonyx jubatus).

An outbreak of vomiting in a group of captive cheetahs (Acinonyx jubatus) was investigated, and histologic examination revealed chronic gastritis characterized by infiltration of lymphocytes and numerous plasma cells and epithelial erosions. Lymphoid follicles, globule leukocytes, scattered neutrophils, and (in one animal) abscessed gastric glands were inconsistent findings. In addition, necropsy of three cheetahs revealed gastric mucosal hyperplasia. Two kinds of bacteria were identified in the stomachs of infected cheetahs. Numerous long, tightly coiled motile Gastrospirillum-like organisms were seen in gastric mucus and in Warthin-Starry-stained sections of mucosa. These bacteria could not be cultured but were transmitted to conventional mice in homogenates of gastric mucosa from infected cheetahs. Ultrastructural examination revealed helical filaments on some of these bacteria. In addition, a smaller Helicobacter sp. was isolated. This organism could be cultured in vitro under microaerophilic conditions. One or both of these bacterial species was probably responsible for the gastritis in these cheetahs.

Acinonyx↗

PubMed1993

Use of a single injection solute-clearance method for determination of glomerular filtration rate and effective renal plasma flow in chickens.

A single-injection clearance method for determining glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) in chickens was compared with the continuous-infusion method. Male and female White Leghorn chickens were anesthetized, and catheters were placed in both brachial veins and over both ureteral openings. A single-bolus injection of 3H-inulin and 14C-para-aminohippuric acid was given at a dose of 1.0 microCi of each solute per kg of body weight and nine blood samples were obtained over 60 min. After the last sample was taken, the birds were given a bolus injection of 1 microCi of 3H-inulin/kg and 1 microCi of 14C-para-aminohippuric acid/kg, followed by a constant infusion of 0.1 microCi of each solute/min at a rate of 0.1 ml.kg-1 x h-1. Following a 45-min stabilization period, three continuous urine collections were performed. A blood sample was obtained at the midpoint of each urine collection. The GFR and ERPF determined by the single-injection method (3.12 +/- 0.43 and 22.81 +/- 3.48 ml.min-1 x kg-1, respectively) were comparable to values for the continuous-infusion method (2.81 +/- 0.35 and 22.88 +/- 4.03 ml.min-1 x kg-1, respectively). Both GFR and ERPF determined by the single-injection method correlated with GFR and ERPF determined by the continuous-infusion method. This single injection method provides a rapid, accurate method for determining GFR and ERPF in chickens and eliminates the need for collection of urine.

Animals↗

PubMed1992

Effects of enalapril and clonidine on glomerular structure, function, and atrial natriuretic peptide receptors in SHHF/Mcc-cp rats.

Seven-month-old, lean male SHHF/Mcc-cp rats, a model of spontaneous hypertension, progressive renal dysfunction, and congestive heart failure (CHF), were treated with either clonidine (CL) or enalapril (EN) or received no treatment (CON) for 20 weeks. CL significantly decreased systolic blood pressure (SBP), kidney weights, and severity of renal lesions as compared with untreated CON. EN produced a decrease in SBP comparable to that in CL. Kidney weights and severity of renal histologic changes in the EN group were intermediate between those of the CL and CON groups. Despite similar plasma atrial natriuretic peptide (ANP) concentrations, CL treatment resulted in a significant increase in the density of guanylate cyclase-linked glomerular ANP receptors, whereas EN treatment resulted in a significant decrease in the total number of ANP receptors and in the number of nonguanylate cyclase-linked receptors and an increase in overall binding affinity. These findings demonstrate that antihypertensive agents will slow progression of renal injury in SHHF/Mcc-cp rats and that CL is more effective than EN in alleviating progressive kidney damage in this model. Furthermore, different classes of antihypertensive drugs may alter the density or ratio of biologically active and clearance ANP receptor sites in the glomerulus.

Animals↗

PubMed1991

Gastric spiral bacilli in captive cheetahs.

Two kinds of gastric spiral bacilli were identified in the stomachs of captive cheetahs with naturally occurring gastritis. One type was morphologically similar to 'Gastrospirillum hominis'. This organism could not be cultured in vitro. Some of these bacteria had superficial helical filaments, and others did not. The other type was morphologically, biochemically, and bacteriologically similar to Helicobacter pylori. This organism is most likely a new species of Helicobacter. One or both of these bacteria may have been responsible for the gastritis seen in these cheetahs.

Acinonyx↗

PubMed1990

Helicobacter pylori gastric infection in gnotobiotic beagle dogs.

Establishment of infection with Helicobacter pylori and gastritis in nonhuman species is currently only successful in gnotobiotic piglets. This study was designed to determine whether H. pylori will colonize the gastrointestinal tract of gnotobiotic dogs. Gnotobiotic beagle pups were derived by standard methods. Group A (five dogs) was orally challenged with 3 x 10(8) H. pylori at 7 days of age. Group B (two dogs) received only peptone water but was contact-exposed beginning on day 23 postinfection (p.i.). Necropsy was performed on dogs on day 30 p.i. H. pylori colonized the stomach of all dogs (groups A and B). Urease map analysis correlated with the microbiologic findings and indicated that the density of colonization was less than that observed in human tissue. Organisms were also recovered from the pharynx, esophagus, duodenum, and rectum of 1, 2, 2, and 1 dog, respectively. All group A and one group B dog developed serum immunoglobulin G specific for H. pylori by day 30 p.i. Gross lesions were restricted to the stomach and consisted of small (less than 1 mm) lymphoid follicles. Microscopically, there were focal to diffuse lymphoplasmacytic infiltrates with follicle formation and mild to moderate infiltration of neutrophils and eosinophils in the gastric lamina propria. With the Warthin-Starry silver stain, organisms were seen on the surface of the gastric epithelial cells, beneath the mucus layer. We conclude that H. pylori colonizes the stomachs of gnotobiotic dogs for at least 1 month and the lesions resemble those seen in humans. H. pylori is transmissible by contact from infected to noninfected dogs.

Animals↗